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Journal of Neuroinflammation

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Open Access 01-12-2012 | Research

Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells

Authors: Jonathan Bertin, Corinne Barat, Dave Bélanger, Michel J Tremblay

Published in: Journal of Neuroinflammation | Issue 1/2012

Abstract

Background

Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS). Leukotriene B₄ (LTB₄) and cysteinyl-leukotrienes such as LTC₄ are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs) in HIV-1 infection of microglial cells.

Methods

To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR).

Results

We report in this study that virus replication is reduced upon treatment of MDMis with LTB₄ and LTC₄. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C.

Conclusions

These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.

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Title: Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells
Authors: Jonathan Bertin
Corinne Barat
Dave Bélanger
Michel J Tremblay
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-9-55

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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